+Open data
-Basic information
Entry | Database: PDB / ID: 8wcc | ||||||
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Title | Cryo-EM structure of the CHA-bound mTAAR1 complex | ||||||
Components | Trace amine-associated receptor 1 | ||||||
Keywords | MEMBRANE PROTEIN / CHA / mTAAR1 | ||||||
Function / homology | Function and homology information G protein-coupled amine receptor activity / Amine ligand-binding receptors / trace-amine receptor activity / G alpha (s) signalling events / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating dopamine receptor signaling pathway / G protein-coupled receptor signaling pathway / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | ||||||
Authors | Rong, N.K. / Guo, L.L. / Zhang, M.H. / Li, Q. / Yang, F. / Sun, J.P. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell / Year: 2023 Title: Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Authors: Pan Shang / Naikang Rong / Jing-Jing Jiang / Jie Cheng / Ming-Hui Zhang / Dongwei Kang / Lei Qi / Lulu Guo / Gong-Ming Yang / Qun Liu / Zhenzhen Zhou / Xiao-Bing Li / Kong-Kai Zhu / Qing- ...Authors: Pan Shang / Naikang Rong / Jing-Jing Jiang / Jie Cheng / Ming-Hui Zhang / Dongwei Kang / Lei Qi / Lulu Guo / Gong-Ming Yang / Qun Liu / Zhenzhen Zhou / Xiao-Bing Li / Kong-Kai Zhu / Qing-Biao Meng / Xiang Han / Wenqi Yan / Yalei Kong / Lejin Yang / Xiaohui Wang / Dapeng Lei / Xin Feng / Xinyong Liu / Xiao Yu / Yue Wang / Qian Li / Zhen-Hua Shao / Fan Yang / Jin-Peng Sun / Abstract: Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment ...Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8wcc.cif.gz | 64.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8wcc.ent.gz | 45.2 KB | Display | PDB format |
PDBx/mmJSON format | 8wcc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8wcc_validation.pdf.gz | 948.7 KB | Display | wwPDB validaton report |
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Full document | 8wcc_full_validation.pdf.gz | 950 KB | Display | |
Data in XML | 8wcc_validation.xml.gz | 21.1 KB | Display | |
Data in CIF | 8wcc_validation.cif.gz | 28.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wc/8wcc ftp://data.pdbj.org/pub/pdb/validation_reports/wc/8wcc | HTTPS FTP |
-Related structure data
Related structure data | 37438MC 8wc3C 8wc4C 8wc5C 8wc6C 8wc7C 8wc8C 8wc9C 8wcaC 8wcbC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 37656.586 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Taar1, Ta1, Tar1, Trar1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q923Y8 |
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#2: Chemical | ChemComp-HAI / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of the CHA-bound mTAAR1 complex / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 1.875 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.20.1_4487: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 296951 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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